Alzheimer-type dementia is characterized in that nerve cell death, neurofibril changes and senile plaque formation occur in the cerebral cortex due to the deposition of extracellular β-amyloid, and atrophy of cerebral cortex, decreased glucose utilization by cerebrum, decreased perfusion in parietal lobe, lateral lobe cortex and prefrontal area cortex, and the like occur, as a result of which a progressive cognitive decline occurs. About 5% of the population aging 65 years or older are considered to be dementia patients, of which 40% is said to be of Alzheimer-type, which is the highest number of patients among the diseases accompanied by disappearance and degeneration of nerve cells, and this disease could be more and more serious in the ageing society in the future.
Therefore, it is difficult for patients with progressed Alzheimer-type dementia to live alone, and the disease lowers the quality of life (QOL) of patients themselves and patients' families taking care of them, and forces a large societal burden in terms of spiritual aspect and economical aspect.
The effect of rivastigmine, i.e., 3-[(1S)-1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate, on Alzheimer-type dementia is considered to be mainly attributable to the inhibition of acetylcholinesterase and butyrylcholinesterase, which increases intracerebral acetylcholine and activates the intracerebral cholinergic nerve system.
Recently, “EXELON PATCH”, which is a patch of rivastigmine, has been placed in the market. This patch preparation has many advantages afforded by not being orally ingested, that side effects such as vomiting and the like can be suppressed, a rapid increase in the blood concentration can be suppressed and the like, since rivastigmine does not go into the stomach directly unlike oral drugs.
However, in the domestic clinical tests of EXELON PATCH, an adverse event such as skin reaction and stimulation at the application site was seen in 663 cases (77.3%) out of 858 cases as the safety analysis subjects, and the skin irritation at the application site poses a problem (non-patent document 1). In particular, many of the Alzheimer-type dementia patients are old. The skin of old person is prone to express skin symptoms more often, since it shows low moisturizing function, gets dry and highly likely shows low skin barrier function due to a decreased production quantity of sebum. When a patch showing skin irritation is adhered to such aged patients, the possibility is extremely high that some harmful phenomenon occurs on the skin.
As a patch containing rivastigmine, a transdermal absorption type preparation containing rivastiyiuine and an antioxidant in a matrix composed of polyacrylate or polymethacrylate (patent document 1), and a transdermal absorption type preparation containing a backing layer (support), a rivastigmine reservoir layer containing polyacrylate, polymethacrylate, polyisobutylene, polybutene, styrene-isoprene-styrene block copolymer and the like, and an adhesion layer containing a silicone polymer and a tackifier (patent document 2) are disclosed. However, the above-mentioned problem of skin irritation of a patch containing rivastigmine has entirely not been solved sufficiently.
On the other hand, as a transdermal absorption type preparation containing other drug, for example, a patch using a rubber-based, acrylate-based or silicone-based adhesion layer is disclosed as a patch of tolterodine, an antimuscarinic drug (patent document 3).
From the aspect of drug stability, moreover, a patch using a rubber-based adhesive showing less interaction with drugs has been proposed (patent documents 4-6).